Do cells sense time by number of divisions?

TL;DR

This paper models telomere length dynamics as a random walk with a potential barrier, explaining how cells can survive many divisions beyond intuitive limits and challenging the idea that cells sense time solely by division count.

Contribution

It introduces a stochastic model of telomere length that accounts for cell survival beyond expected division limits, highlighting the role of telomerase and potential barriers in cell lifespan regulation.

Findings

Telomere length exhibits a two-phase behavior: deterministic drift and stochastic fluctuations.

The model predicts a quasi-equilibrium state where telomere length persists before senescence.

Telomerase creates a potential barrier that extends cell survival by stabilizing telomere length.

Abstract

Do biological cells sense time by the number of their divisions, a process that ends at senescence? We consider the question "can the cell's perception of time be expressed through the length of the shortest telomere?" The answer is that the absolute time before senescence cannot be expressed by the telomere's length and that a cell can survive many more divisions than intuitively expected. This apparent paradox is due to shortening and elongation of the telomere, which suggests a random walk model of the telomere's length. The model indicates two phases, first, a determinist drift of the length toward a quasi-equilibrium state, and second, persistence of the length near an attracting state for the majority of divisions prior to senescence. The measure of stability of the latter phase is the expected number of divisions at the attractor ("lifetime") prior to crossing a threshold to senescence. The telomerase regulates stability by creating an effective potential barrier that separates statistically the shortest lifetime from the next shortest. The random walk has to overcome the barrier in order to extend the range of the first regime. The model explains how random telomere dynamics underlies the extension of cell survival time.